Immunological aspects of aging and various age-related diseases, including neoplasia, will be investigated with an experimental system involving inbred rats. Studies will be undertaken correlating the biological activity in vivo of immunocompetent lymphocytes responsive to major histocompatibility differences (H-ARC) with the age of the animal, and with the incidence of neoplasia and other disorders such as chronic respiratory disease, both in different rat strains and in the same strain before and after the onset of the disease condition. The numbers of these lymphocytes (H-ARC), their turnover rate in vivo, and their proliferative behavior following stimulation with allogeneic cells in short-term mixed cultures (MLI) will be investigated. Rats will be injected with tritiated thymidine and subsequently blood smears and mixed lymphocyte cultures (MLI) will be examined for frequency of labelled cells and for grain count data. In addition to correlations of H-ARC activity with age and disease, specific efforts will be made to determine if H-ARC proliferation in vivo is normally antigen-driven, and the nature of the antigenic stimulus. Evidence will be sought to support or deny the premise that the cells of the circulating lymphocyte pool reactive to the major H alloantigens of the species are involved in an immunologically mediated surveillance mechanism against neoplasia. BIBLIOGRAPHIC REFERENCES: Heber-Katz, E., and D.B. Wilson. Collaboration of allogeneic T and B lymphocytes in the primary antibody response to sheep erythrocytes in vitro. In Mitogens in Immunobiology. (ed. J.J. Oppenheim and D.L. Rosenstreich) Academic Press, New York, 1976, p. 375. Wilson, D.B., A. Marshak, and J.C. Howard. Specific positive and negative selection of rat lymphocytes reactive to strong histocompatibility antigens. Activation with alloantigens in vitro and in vivo. J. Immunol. 116:1030, 1976.